Biomedical subjects

Zhonghua Liu

Publications and source records attributed to Zhonghua Liu.

4 recordsLinked to original sources

PubMed2026

Cross-ancestry proteome-wide Mendelian randomization prioritizes 12 plasma protein candidates for breast cancer risk.

The plasma proteome provides a molecular bridge between genetic variation and disease risk, yet its contribution to breast cancer susceptibility across ancestries remains unclear. We conducted a proteome-wide Mendelian randomization (MR) study of 2,923 plasma proteins using cis-protein quantitative trait loci from 34,557 European participants in the UK Biobank Pharma Proteomics Project, integrated with genome-wide association studies of 156,901 breast cancer cases and 204,634 controls of European, East Asian, and African ancestries. Cross-ancestry meta-analysis identified 12 candidate proteins associated with breast cancer risk (P < 2.5×10-5), including six previously reported and six newly implicated in MR studies. DNPH1 showed cross-ancestry heterogeneity, with a risk-increasing association in European populations and a nominally inverse association in East Asian populations. CASP8, RALB, and USP28 displayed subtype-differentiated associations. Orthogonal validation provided variable support: six demonstrated strong evidence of statistical colocalization; four replicated in an independent European proteomic dataset (deCODE, n = 35,559); two replicated in an independent East Asian proteomic dataset (JCTF, n = 1,384); and four were supported by polygenic-score analyses in the ancestrally diverse All of Us cohort (9,250 cases, 214,857 controls). These findings prioritize a high-confidence subset of plasma proteins, including LRRC25, PARK7, and LRRC37A2, for future mechanistic and translational investigation.

Mendelian randomization↗

PubMed2025

A long noncoding RNA with enhancer-like function in pig zygotic genome activation.

The zygotic genome activation (ZGA) is crucial for the development of pre-implantation embryos. Long noncoding RNAs (lncRNAs) play significant roles in many biological processes, but the study on their role in the early embryonic development of pigs is limited. In this study, we identify lncFKBPL as an enhancer-type lncRNA essential for pig embryo development. lncFKBPL is expressed from the 4-cell stage to the morula stage in pig embryos, and interference with lncFKBPL leads to a developmental arrest at the 8-cell stage. Mechanistic investigations uncover that lncFKBPL is able to bind to MED8, thereby mediating enhancer activity and regulating FKBPL expression. Additionally, FKBPL interacts with the molecular chaperone protein HSP90AA1, stabilizing CDK9 and boosting its protein-level expression. Elevated CDK9 levels enhance Pol II phosphorylation, facilitating ZGA. Our findings illuminate the role of lncFKBPL as an enhancer lncRNA in pig ZGA regulation and early embryo development, providing a foundation for further exploration in this area.

Animals↗

PubMed2025

CsMYB219 and CsMYB196 influence epigallocatechin gallate biosynthesis in tea plant (Camellia sinensis) by regulating CsSCPL1A gene expression.

Epigallocatechin gallate (EGCG) is the most abundant and biologically active catechin in tea leaves and has been widely utilized in the development of functional foods. EGCG is catalyzed by serine carboxypeptidase-like 1A (CsSCPL1A) acyltransferases in tea plants. Although CsSCPL family genes are regulated by several transcription factors (TFs), systematic studies on their regulation by MYB TFs are lacking. This study integrates targeted metabolomics, transcriptomics, DNA-protein, and protein-protein interaction analyses to elucidate the transcriptional regulation of EGCG biosynthesis-related genes CsSCPL4 and CsSCPL5-1 by R2R3-MYB TFs. CsMYB219 and CsMYB196 can specifically bind to CsSCPL4 and CsSCPL5-1 promoters and activate their expression. CsMYB196 also interacted with CsTT8a and CsTTG1 to activate the transcription activity of CsSCPL4 and CsSCPL5-1 promoters by forming a MYB/bHLH/WD40 (MBW) complex. Promoter truncation assays delineated MYB-responsive cis-elements in CsSCPL4 (-613 to -1 bp with enhancers at -1967 to -1622) and CsSCPL5-1 (-503 to -296 bp). Silencing of CsMYB219 and CsMYB196 by virus-induced gene silencing (VIGS) assay significantly reduced the expression levels of CsSCPL4 and CsSCPL5-1 and EGCG content in tea leaves. Transient overexpression of CsMYB219 and CsMYB196 in tea leaves upregulated CsSCPL4 and CsSCPL5-1 expression and elevated EGCG content. These findings enhance our understanding of the regulatory network underlying EGCG biosynthesis in tea plants and provide a solid foundation for future genetic improvement of tea plant cultivars.

Catechin↗

PubMed2024

Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data.

Causal mediation analysis provides an attractive framework for integrating diverse types of exposure, genomic, and phenotype data. Recently, this field has seen a surge of interest, largely driven by the increasing need for causal mediation analyses in health and social sciences. This article aims to provide a review of recent developments in mediation analysis, encompassing mediation analysis of a single mediator and a large number of mediators, as well as mediation analysis with multiple exposures and mediators. Our review focuses on the recent advancements in statistical inference for causal mediation analysis, especially in the context of high-dimensional mediation analysis. We delve into the complexities of testing mediation effects, especially addressing the challenge of testing a large number of composite null hypotheses. Through extensive simulation studies, we compare the existing methods across a range of scenarios. We also include an analysis of data from the Normative Aging Study, which examines DNA methylation CpG sites as potential mediators of the effect of smoking status on lung function. We discuss the pros and cons of these methods and future research directions.

causal inference↗